AveXis Reports Data from Ongoing Phase 1 Trial of Gene Therapy in Spinal Muscular Atrophy Type 1

AveXis, a clinical-stage gene therapy company developing novel treatments for patients suffering from rare and life-threatening neurological genetic diseases, presented an interim analysis of data from the ongoing Phase 1 trial of AVXS-101 for the treatment of spinal muscular atrophy (SMA) Type 1. Jerry Mendell, MD, director of the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, presented the data at the 19th Annual Meeting of the American Society of Gene & Cell Therapy in Washington, D.C.

The data reported at the meeting show that AVXS-101 continues to demonstrate a favorable safety profile in patients studied, with no new treatment-related safety or tolerability concerns identified; all patients in both the low-dose and proposed therapeutic-dose cohorts remain without an “event,” defined as death or until a patient requires at least 16 hours per day of ventilation support for breathing for 14 consecutive days in the absence of an acute reversible illness, or perioperatively; and the mean motor function score continues to increase, with two patients having achieved motor function in a range considered to be normal.

Dr. Mendell said, “Given the rapid and devastating disease course of SMA Type 1, it is very encouraging to see that all patients in both dosing cohorts have remained event free, and all patients have demonstrated sustained improvements above baseline in motor function since receiving AVXS-101.  Additionally, new data presented today appear to indicate that AVXS-101 may have a positive impact on both the pulmonary and nutritional support of patients in the trial suffering from SMA Type 1, which may be impacting the overall survival benefit.”

The ongoing Phase 1 study is designed to evaluate safety and preliminary indications of efficacy of AVXS-101 in patients suffering from SMA Type 1. Data as of April 1, 2016 has shown:

• AVXS-101 appears to have a favorable safety profile and to be generally well tolerated in patients studied. There has been a total of 74 adverse events (AEs) reported, 22 of which were determined to be serious adverse events (SAEs). Two of the 22 were deemed treatment-related and, as previously reported, those SAEs were clinically asymptomatic liver enzyme elevations. Of the 52 non-serious AEs, 3 were treatment-related elevations in liver enzymes experienced by two patients. All elevated liver enzyme AEs and SAEs were resolved with prednisolone treatment. Other non-treatment-related AEs were expected and were associated with SMA.
• No patients in either dosing cohort have experienced an “event.” The median event-free age of all 15 patients was 14.9 months, and the median event-free age of patients in Cohort 1 was 25.7 months and in Cohort 2 was 11.7 months. The natural history of the disease indicates that 25 percent of untreated SMA Type 1 patients survive event-free at 13.6 months of age and that 8 percent survive event-free at 20 months of age1.
• Mean increases of 8.7 points and 19.2 points in CHOP-INTEND scores were observed in Cohort 1 and Cohort 2, respectively. Nine out of 12 patients (75 percent) and 7 out of 12 patients (58 percent) in Cohort 2 have achieved CHOP-INTEND scores of at least 40 points or 50 points, respectively. Two patients achieved the maximum score of 64. A score of 60 is considered normal. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) is a test developed to measure motor skills of patients with SMA Type 1.
• The natural history of SMA Type 1 indicates that bulbar weakness leads to impaired swallowing, malnutrition and growth failure. The median age to growth failure is 7 months of age2. The median age to nutritional support is 8 months of age (IQR 6-13 months)1. AVXS reported today that 7 of 7 (100%) of AVXS-101 patients that did not require feeding support before treatment continued without feeding support as of April 1, 2016 in the ongoing Phase 1 trial. Five patients had gastric feeding tube placement prior to gene therapy. One patient in Cohort 2 who had gastric feeding tube placement prior to gene transfer is also feeding orally.
• The natural history of SMA Type 1 indicates that bulbar muscle weakness, skeletal muscle weakness in the neck and intercostal muscle weakness lead to respiratory impairment, poor clearance of airway secretions, risk of aspiration and recurrent infections leading to death or permanent ventilation. The median age to permanent ventilation or death is 10.5 months (IQR 8.1-13.6 months), and by 13.6 months only 25 percent of SMA Type 1 patients are alive and free of permanent ventilation1. In the ongoing trial, 8 of 10 (80%) of AVXS-101 patients that did not use biphasic/bi-level ventilation (BiPAP) support before gene transfer continue without any ventilation support as of April 1, 2016 (the 2 exceptions being after severe illness/hospitalizations to assist recovery).

“We are encouraged by these interim results as we work diligently to bring AVXS -101 to patients who suffer from SMA Type 1, a devastating disease for which there are currently no FDA-approved therapies,” said Suku Nagendran, MD, Senior Vice President and Chief Medical Officer, AveXis. “We look forward to reviewing the ongoing data from this study over the coming year as we continue the development of AVXS-101.”